RGD Reference Report - Estrogen receptor 1 polymorphisms are associated with airway hyperresponsiveness and lung function decline, particularly in female subjects with asthma. - Rat Genome Database

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Estrogen receptor 1 polymorphisms are associated with airway hyperresponsiveness and lung function decline, particularly in female subjects with asthma.

Authors: Dijkstra, A  Howard, TD  Vonk, JM  Ampleford, EJ  Lange, LA  Bleecker, ER  Meyers, DA  Postma, DS 
Citation: Dijkstra A, etal., J Allergy Clin Immunol. 2006 Mar;117(3):604-11. Epub 2006 Feb 15.
RGD ID: 4892312
Pubmed: PMID:16522460   (View Abstract at PubMed)
DOI: DOI:10.1016/j.jaci.2005.11.023   (Journal Full-text)

BACKGROUND: Sex hormones may contribute to the higher prevalence and severity of adult asthma in women compared with men. OBJECTIVE: Sequence variants in the estrogen receptor alpha gene (ESR1) may alter estrogen action in asthma. METHODS: Two hundred asthma probands and their families (n=1249) were genotyped for 5 single nucleotide polymorphisms (SNPs) in the ESR1 gene (intervening sequence 1 [IVS1]-1505A/G, IVS1-1415T/C, IVS1-397C/T, IVS1-351G/A and exon1+30T/C). Association with asthma and bronchial hyperresponsiveness (BHR) were tested. In the asthma probands, association of SNPs with BHR severity and annual FEV1 decline were determined. RESULTS: No SNP was associated with asthma. IVS1-397 was significantly associated with the presence of BHR (P=.02) and interacted with sex; female subjects with the CT or TT genotype were at risk (P=.01). In asthma probands, all SNPs were associated with FEV1 decline. Exon1+30 CT and TT group had an excess decline of 11.6 mL/y (P=.03) and 15.7 mL/y (P=.01), respectively, compared with the CC group. Of the IVS1 polymorphisms, IVS1-351G/A showed the strongest association, with the AA group having excess decline of 16.1 mL/y (P=.01) compared with the GG group. In subanalyses by sex, these associations were significant only in female subjects. CONCLUSION: ESR1 gene variants may affect development of BHR, particularly in female subjects. They may also lead to a more rapid lung function loss in patients with asthma, and in female subjects specifically. This may result from altered estrogen action, which affects lung development and/or airway remodeling. Further studies on ESR1 gene variations are important to understand better the origin of sex differences in asthma. CLINICAL IMPLICATIONS: Variations in the gene encoding estrogen receptor alpha are associated with BHR and a more rapid annual lung function decline, especially in female subjects. Even though this has no diagnostic or clinical implication, it may open avenues for future sex-specific treatment in asthma.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Bronchial Hyperreactivity  IAGP 4892312 RGD 
Bronchial Hyperreactivity  ISOESR1 (Homo sapiens)4892312; 4892312 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Esr1  (estrogen receptor 1)

Genes (Mus musculus)
Esr1  (estrogen receptor 1 (alpha))

Genes (Homo sapiens)
ESR1  (estrogen receptor 1)


Additional Information